Cesium carbonate → Methyl 3-(2-chlorophenyl)-1-(4-methylphenyl)-1H-indole-6-carboxylate

HRID 1047649Notes

Reaction equation

HRID 1047649 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11](=[O:13])C)=[CH:8][CH:9]=2)[N:4]([C:14]2[CH:19]=[CH:18][C:17]([CH3:20])=[CH:16][CH:15]=2)[CH:3]=1.[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1B(O)O.[C:31](=O)([O-])[O-:32].[Cs+].[Cs+]>[Cu]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:2]1[C:10]2[C:5](=[CH:6][C:7]([C:11]([O:32][CH3:31])=[O:13])=[CH:8][CH:9]=2)[N:4]([C:14]2[CH:15]=[CH:16][C:17]([CH3:20])=[CH:18][CH:19]=2)[CH:3]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27343222-Chlorophenylboronic acidHCID 666614541-[3-bromo-1-(4-methylphenyl)-1H-indol-6-yl]ethanone

Product 1

HCID 66661407Methyl 3-(2-chlorophenyl)-1-(4-methylphenyl)-1H-indole-6-carboxylateYield 94.4%

Reagents, catalysts & solvents 4

HCID 62652Cuprous chlorideCatalystHCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 1-[3-bromo-1-(4-methylphenyl)-1H-indol-6-yl]ethanone (0.11 g, 0.31 mmol), 2-chlorophenylboronic acid (73.9 mg, 0.47 mmol), cesium carbonate (0.31 g, 0.94 mmol), copper(I) chloride (32.8 mg, 0.33 mmol), 1,1′-bis(diphenylphosphino)ferrocene (18.6 mg, 34.0 μmol) and palladium(II) acetate (3.5 mg, 16.0 μmol) under Ar was added N,N-dimethylformamide (4.3 mL). The mixture was stirred in a sealed tube at 90° C. for 30 min. The mixture was cooled to ambient temperature and quenched with saturated aqueous sodium bicarbonate (1×15 mL). The mixture was extracted with ethyl acetate (3×15 mL). The combined organic layer was washed with saturated aqueous sodium chloride (1×10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate) gave the title compound (0.11 g): LC-MS [M+1]=376.0.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customquenched with saturated aqueous sodium bicarbonate (1×15 mL)
  3. extractionThe mixture was extracted with ethyl acetate (3×15 mL)
  4. washThe combined organic layer was washed with saturated aqueous sodium chloride (1×10 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customPurification by silica gel chromatography (100% hexanes→95% hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-925dcc40b11941738ea1b29786935175
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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